The goal of this project is to develop a new technology for the rapid screening and analysis of cancer-linked proteins. AmberGen has made significant progress during Phase I by developing methods for the rapid isolation, detection and analysis of proteins. Referred to as Pro-Screen (protein screening), the technology is based on the use of tRNAs to incorporate special markers and linkers into proteins which are expressed in vitro from a patient's genomic DNA or mRNA. Specific accomplishments include demonstration of the ability to rapidly detect truncations, point mutations and functional defects. During Phase II, AmberGen will shift its focus towards clinical applications. Highly sensitive, rapid and non-isotopic methods will be introduced for detecting chain-truncating mutations based on fluorescent-PAGE and chemiluminescence. Rapid screening of point mutations will be facilitated using UV -MALDI mass spectrometry. A variety of rapid functional assays of cancer-linked proteins will be developed which are based on in vitro incorporation of multiple markers. Clinical applications to be evaluated include the detection of APC mutations in familial adenamatous polyposis (FAP); the screening of APC and p53 mutations as part of a non-invasive diagnostic assay for colorectal cancer and the profiling of p53 mutations in lung and breast solid-tumors. PROPOSED COMMERCIAL APPLICATION: AmberGen will commercialize Pro-Screen technology with specific applications in the area of pharmaceutical genomics, screening of inherited diseases, early detection of cancers and profiling of tumors for clinical diagnosis. An early focus of commercialization will be the introduction of screening technology to detect APC and p53 mutations as part of a non-invasive colorectal cancer test as well as BRCA screening. Subsequently, several cancer related genes would be screened using AmberGen's Pro-Screen technology.